Prospective, Longitudinal Study of Cancer Predictors and Rates in a New York City Cohort of 598 Patients With Acromegaly

Context: Long-term growth hormone/insulin-like growth factor-1 (GH/IGF-1) excess could increase the risk of cancer in acromegaly, but individual levels of these hormones do not relate to this risk. Objective: We newly investigated longitudinally-measured IGF-1 levels as a potential predictor of cancer in a large New York City acromegaly cohort. Methods: We conducted a prospective, longitudinal study of 598 acromegaly (309 men, 289 women) and 292 clinically nonfunctioning pituitary adenoma (CNFPA) (140 women, 152 men) patients from the same underlying population. GH and IGF-1 levels were measured longitudinally and outcomes were observed during long-term follow-up. Cumulative exposure to IGF-1 excess was tested as a predictor of cancer. We compared cancer prevalence in acromegaly and CNFPA cohorts and incidence in each to that expected from Surveillance, Epidemiology, and End Results (SEER) data. Results: Cancer prevalence by last follow-up was 22.6% in acromegaly and 12.7% in CNFPAs (odds ratio [OR] = 1.99 [95% CI, 1.34-2.97]) (P = .0005). Overall standardized incidence ratio for cancer was 1.78 (1.51-1.81) in the acromegaly and 1.26 (0.89-1.70) in the CNFPA cohorts. Cumulative exposure to IGF-1 excess, OR = 1.278 (1.060-1.541) (P = .01), years from acromegaly diagnosis to cancer or last follow-up, OR = 1.03 (1.004-1.057) (P = .024), and age at follow up, OR = 1.064 (1.047-1.082) (P < .001), were predictors of cancer. Conclusion: Cancer risk is increased in acromegaly, but not in CNFPA patients. Cumulative exposure to IGF-1 excess is a predictor of cancer in acromegaly. Our data suggest that cancer risk in acromegaly relates to the degree and duration of IGF-1 excess and that full appreciation of this risk requires long-term follow up.